Immunoregulation by lipids during the development of non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) represents the most common liver disorder inwestern countries and it is commonly associated with obesity and progression of the metabolic syndrome.Comprehending a wide spectrum of pathologic features, it is currently well recognized that a key point forthe integrity of hepatocyte functionality in NAFLD is the progression from simple steatosis to non-alcoholicsteatohepatitis (NASH). Indeed, activation of the innate immune system in response to hepatic metabolicstresses represents a central process that determines the evolution and the reversibility of liver damage.Despite of the burden of studies published in recent years, it is still intriguingly unclear how accumulationof lipids in hepatocytes triggers the activation of the inflammatory response leading to the recruitment ofinfiltrating cells of extra-hepatic origins. In this review we offer a general view on recent advances pointingout how different classes of lipids are able to specifically affect hepatocytes functionality and survival, thusdifferently influencing the organization of the hepatic immune response. On the other hand, we gatheredrecent studies intending to illustrate the basic mechanisms through which several non-parenchymal hepaticand extra-hepatic cell populations get activated in response to lipids. Finally, we indicate latter findingsproposing how the immune system majorly contributes to the progression of NASH.